Novel associations between CYP2B6 polymorphisms, perioperative methadone metabolism and clinical outcomes in children-Reference-Cited by-同舟云学术

Novel associations between CYP2B6 polymorphisms, perioperative methadone metabolism and clinical outcomes in children

Published:2021-07 Issue:10 Volume:22 Page:591-602
ISSN:1462-2416
Container-title:Pharmacogenomics
language:en
Short-container-title:Pharmacogenomics

Author:

Packiasabapathy Senthil¹^ORCID,Aruldhas Blessed W¹²³^ORCID,Zhang Pengyue⁴,Overholser Brian R²⁵^ORCID,Quinney Sara K²⁶⁷^ORCID,Sadhasivam Senthilkumar¹^ORCID

Affiliation:

1. Department of Anesthesia, Indiana University School of Medicine, Indianapolis, IN 46202, USA

2. Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN 46202, USA

3. Department of Pharmacology & Clinical Pharmacology, Christian Medical College, Vellore, 632 004, India

4. Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN 46202, USA

5. Department of Pharmacy Practice, Purdue University College of Pharmacy, Indianapolis, IN 46202, USA

6. Department of Obstetrics & Gynecology, Indiana University School of Medicine, Indianapolis, IN 46202, USA

7. Center for Computational Biology & Bioinformatics, Indiana University School of Medicine, Indianapolis, IN 46202, USA

Abstract

Aim: Methadone exhibits significant variability in clinical response. This study explores the genetic influence of variable methadone pharmacokinetics. Methods: This is a prospective study of methadone in children undergoing major surgery. CYP2B6 genotyping, plasma methadone and metabolite levels were obtained. Clinical outcomes include pain scores and postoperative nausea and vomiting (PONV). Results: CYP2B6 poor metabolizers (*6/*6) had >twofold lower methadone metabolism compared with normal/rapid metabolizers. The incidence of PONV was 4.7× greater with CYP2B6 rs1038376 variant. AG/GG variants of rs2279343 SNP had 2.86-fold higher incidence of PONV compared with the wild variant ( AA). Nominal associations between rs10500282, rs11882424, rs4803419 and pain scores were observed. Conclusion: We have described novel associations between CYP2B6 genetic variants and perioperative methadone metabolism, and associations with pain scores and PONV.

Funder

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

Link

https://www.futuremedicine.com/doi/pdf/10.2217/pgs-2021-0039

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